The typical manner of administering drugs and dyes to the body is via injection into the bloodstream or a localized area in the body. When injected into the bloodstream, the injected material is carried throughout the blood system and therefore the entire body. This is known as a systemic delivery. The drawbacks to this delivery system are that the concentration of the injected material is extremely diluted and the material acts on most tissues in the body and may be toxic to some of them. In addition, the location and duration of exposure of these injected materials cannot be controlled.
In a localized injection, the location is controlled. Certain organs of the body, such as the eye, cannot be invaded, at least for diagnostic purposes, and local injections are thus not feasible. A sharp, easily visible wavefront of dye or drug, known as a bolus, can be achieved by controlling the injection in the vein. However, a bolus cannot be obtained repeatedly because the material already injected accumulates, causing a background and limiting the dose. Repeated boli can be important where physiological conditions, such as exercise, breathing of oxygen, and sugar level, are altered between them for diagnostic purposes.
In an effort to overcome some of the drawbacks of systemic and local injections of drugs and dyes, lipid vesicles, known as liposomes, have come into use in recent years. The lipid vesicles encapsulate drugs or dyes and can be injected into the bloodstream where they are carried to various organs in which they are naturally ruptured and the encapsulated materials released. The manner of making lipid vesicles is disclosed in, for example, U.S. Pat. No. 4,078,052 to Papahadjopoulos and U.S. Pat. No. 4,241,046 to Papahadjopoulos et al, the disclosures of which are hereby incorporated by reference. While the use of lipid vesicles can improve drug and dye delivery, they also have drawbacks. Thus, traditionally, the concentration of the released encapsulated material and the location and duration of such release cannot be controlled.
In an attempt to obtain some control of the location at which material encapsulated by lipid vesicles is released, microwaves have been applied to heat specific tissue areas after heat-sensitive lipid vesicles have been systemically injected. While these attempts have provided some limited benefits, they likewise have significant drawbacks. First, microwaves have long wavelengths and therefore cannot be narrowly focused to a narrow spot which would be required in treating small vessels and areas of the body. Second, since microwaves cannot be narrowly focused, they tend to heat additional areas of surrounding tissue which may cause damage. Third, microwaves affect the liposomes and the tissue equally by heating up both. Finally, since microwaves have a wavelength in the invisible part of the electromagnetic spectrum, they cannot be observed upon delivery and it is difficult to know whether the microwaves have been properly aimed at the targeted tissue.
Examples of various patents relating to the use of lipid vesicles for delivery of material in the body are disclosed in U.S. Pat. No. 4,310,506 to Baldeschwieler et al; U.S. Pat. No. 4,350,676 to Laties et al; U.S. Pat. No. 4,515,736 to Deamer; U.S. Pat. No. 4,522,803 to Lenk et al; and U.S. Pat. No. 4,610,868 to Fountain et al, the disclosures of which are hereby incorporated by reference.
Examples of the use of heat to release material encapsulate in lipid vesicles, including the use of microwaves, are disclosed in the following publications: Yatvin et al, Design of Liposomes for Enhanced Local Release of Drugs by Hyperthermia, Science, Vol. 202, pp. 1290-1292, Dec. 22, 1978; Weinstein et al, Liposomes and Local Hyperthermia: Selective Delivery of Methotrexate to Heated Tumors, Science, Vol. 204, pp. 188-191, Apr. 13, 1979; Weinstein et al, Treatment of Solid L1210 Murine Tumors with Local Hyperthermia and Temperature-Sensitive Liposomes Containing Methotrexate, Cancer Research, Vol. 40, pp. 1388-1394, May, 1980; and Weinstein et al, Phase Transition Release, A New Approach to the Interaction of Proteins with Lipid Vesicles, Application to Lipoproteins, Biochimica et Biophysica Acta, Vol. 647, pp. 270-284, 1981. In addition, U.S. Pat. No. Re. 32,066 to Leveen discloses the use of radio frequency electromagnetic radiation for treating tumors.